We will analyse further the bases for increased autoimmunity in patients with primarily, generally genetically, determined immunodeficiency, especially patients who have selective absence of IgA. We will also attempt to determine whether immunodeficiency and autoimmunity accompany senile dementia of the Alzheimer type as they do Down's syndrome. In addition we plan to analyse critically the observation that calorie restriction prolongs life, inhibits development of autoimmunity and inhibits development of cardiovascular and renovascular lesions. We intend to determine whether calorie or dietary constituents manipulation can induce or alter the expression of amyloid deposits, fibrillary tangles and plaque formation in the mouse brain.